Although it can be hypothesized that brain alterations

Although it can be hypothesized that THZ1 Hydrochloride Supplier alterations also play a role in the complex persistent complaints of patients with chronic whiplash-associated disorders (WAD), these changes remain poorly investigated. Therefore, the , recently published in , is of great scientific and clinical importance because they examined possible alterations in regional cerebral blood flow (rCBF) in female patients with chronic WAD (n=12) compared to healthy pain-free women (n=8) by using HO positron emission tomography (PET). Brain function, which reflects the amount of ‘activity’ that the brain generates, can be measured via its blood perfusion and/or metabolism by using PET with intravenous injection of a radiopharmaceutical tracer such as HO (). Active brain regions have a higher need of oxygen and glucose, which is reflected in higher perfusion and/or metabolism. The present commentary article focuses on the contribution of the study of to the literature, discusses the paper in the context of current research, highlights unanswered questions and addresses recommendations for future research. The case-control study of correctly raises our attention to the necessity of examining brain alterations in chronic WAD, which is a prominent gap in current literature. Nevertheless, reorganization of the brain is possibly the missing cornerstone for understanding the pathophysiology of chronic WAD and for advancing pain treatment. The authors hypothesized that the close interaction between the neck and midbrain structures through fibers originating from the C1–C3 spinal segments that project to the periaqueductal grey (PAG) and the thalamus () could be the missing key. We believe this is indeed one possible piece of the puzzle for understanding chronic WAD, however, we want to alert that also alterations in (resting state) functional brain connectivity and activity, and structural alterations in cortical and subcortical grey matter regions and white matter tracts could contribute to chronic pain and associated complaints in these patients. In contrast to their hypothesis, Vállez García et al. could not detect significant alterations in rCBF in the PAG (), which is a midbrain structure believed to be involved in brain-orchestrated descending pain modulation (). Nevertheless, this hypothesis is plausible, as dysfunctional pain modulation is a key symptom of patients with chronic WAD. On the contrary, the authors demonstrated altered rCBF in limbic () and corticolimbic () brain regions and regions that are involved in various aspects of pain processing (). Previous brain imaging studies in other chronic musculoskeletal pain patients such as chronic low back pain and fibromyalgia have likewise observed functional but also structural alterations in these regions (e.g. thalamus, insula, precuneus, parahippocampal and posterior cingulate gyrus) compared to controls (). Furthermore, Vállez García et al. correlated the rCBF of the regions that presented significant perfusion differences with subjective scores on the Neck Disability Index (NDI), Hospital Anxiety and Depression Scale (HADS), Whiplash Disability Questionnaire (WDQ), and the electrical perception and pain thresholds measured at the second and sixth cervical spinal processes (). This is important as these measures represent subjective pain experience and are cost-effective in the context of clinical practice. The authors reported significant correlations between the rCBF in the right precuneus, right insula, and right superior temporal lobe, although to different extents, with the scores obtained from the NDI, HADS, WDQ and the electrical perceptions and pain thresholds (both positive and negative correlations) in the chronic WAD group. However, it is not clear from the manuscript if these are weak, moderate or strong correlations. Yet, the observed correlations are of clinical importance because they emphasize the existence of a relationship between clinical symptoms in chronic WAD patients and regional perfusion alterations in the brain.